The experiments proposed in this grant will provide new information concerning sarcomere mechanics in the heart. These experiments will utilize recently developed techniques which allow direct control of the internal ionic environment and sarcomere spacing of cardiac muscle cells. The techniques, employing both muscle disruption and laser light diffraction, are very useful in examining sarcomere mechanics in the heart, since it is possible to measure sarcomere force and velocity when both Ca 2 ion-activation of contraction and sarcomere length are controlled. We proposed to use the above techniques to examine systemically the separate and interactive relationships between force, sarcomere velocity, sarcomere length and Ca 2 ion in guinea pig ventricular muscle. Specific proposals include: deriving the Ca 2 ion isometric tension relation at various mean sacrcomere lengths; studying sarcomere velocity as a function of applied load (developed muscle force), intracellular free Ca 2 ion concentration, and initial mean sarcomere length; examining the sarcomere length-tension relation at various Ca 2 ion concentrations and at various ionic strengths; and finally, examining the sarcomere velocity-force relation at various Ca 2 ion concentrations, initial mean sarcomere lengths, and ionic strengths. These experiments should provide new information and insight into the primary factors involved in modulating sarcomere velocity during isotonic contractions in the heart, particularly resistive or restoring forces, dependent on sarcomere length or ionic strength, which influence Ca 2 ion activated tension development.